Repeated abuse of methamphetamine (MA) results in schizophrenia-like psychosis in human, and this abuse produces behavioral sensitization and neurotoxicity in animals. Understanding of neuropharmacology of MA may provide insight into the pathogenesis of both MA-induced psychosis and schizophrenia. This research examined a role of nitric oxide (NO) synthesis in behavioral sensitization to MA and MA-induced neurotoxicity.1) NO synthase inhibitor reduced the behavioral changes induced by a single administration of MA.2) NO synthase ingibitor had no effect on MA-induced DA release in the striatum.3) NO synthase inhibitor reduced the degree of the sensitization to MA-induced stereotypy.4) NO synthase inhibitor attenuated the MA-induced dopaminergic neurotoxicity in the striatum.Taken together, these results suggest that NO synthesis play a role in MA-induced acute behavioral changes and the development of behavioral sensitization to MA.Furthermore, NO synthesis has been suggested to be related to MA-induced neurotoxicity.以上より、NO産生はDA系神経伝達とは別の経路あるいはDAによるDA受容体刺激以後の神経伝達過程を介して覚醒剤の急性行動効果発現に関与し、常同行動に対する行動感作形成にも影響することが明らかになった。さらに、NO産生は覚醒剤大量投与による線条体DA神経毒性にも関与することが明らかになった。